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7/4/2011 3:57:00 AM

Physiology Lecture 23

Principles of countercurrent multiplication and exchange,

this is how the kidney forms a concentrated or dilute

urine. We had talked about last week when we looked at

bp regulationhow ADH was involved in changing water

permeability properties of the collecting duct. And so

when ADH was around that opened up aquaporin

channels produced more aquaporin channels in the

princilpal cells of the collecting duct so water could leave

the tubular fluid within the collecting duct and go into the

interstitial space, be absorbed by the vasa recta and

carried back to the body. So our question today is how

does that water reabsorption occur, why does water

leave the collecting duct. Were going have to look at

the anatomical and functional relationships btwn the loop

of henle, collecting duct, and the vasa recta.

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So 1stwere going to look at what osm and volume

changes occur along the renal tubule. When ADH is

around?

Loop of Henle and collecting duct work together to form a

concentrated urine, or establish the environment to do

that.

Diff btwn countercurrent multiplication which is the thing

that happens w/ loop of henle, and countercurrent

exchange which is something that happens w/ the vasa

recta.

Finally well look at things that may alter your ability to

form a concentrated urine.

So.

We have the outer section of kidney cortex, proximal

tubule, distal, and parts of the collecting duct. Then we

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have a medullary portion deeper inside kidney: loop of

henle, medullary portion of the collecting duct.

Insterstitial osmolarity it starts out at around 300. It

starts out at 300 in the cortex of the kidney,the

instersituium is that space that surrounds the cells but its

not within the blood vessel, space btwn cells and bvs.

600

1200

Osmolarity of that insterstitial space changes from being

isotonic in the cortex to hypertonic down at the base of

the loop of henle.

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These diagrams in physiology and histology are

misleadingthese tubules are packed together (handful

of pens).

If you look at ends of these, there is space in btwn each

of these tubes, and thats the interstitial space. Tightly

packed, IS surrounds every one of these tubules.

See thin ascending , thin descending, collecting duct,

depending on section.

Packed real close together, so numbers are the same

everywhere (osm numbers).

Fluid coming in from glomerular capillary is essentially

isotonic w/ blood and so the Na , K , bi carb , etc

Concentrations are the same as in tubular fluid as in

glomerulary capillary. Through a variety of Na

cotransport, countertransport processes, Na is

reabsorbed and because the proximal tubule is very

permeable to water, water follows. And out here is the

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peritubular capillary bed , osmotic oncotic and

hydrostatic pressure within this peritubular bed favored

continued water reabsorption, so water leaves and goes

into IS. So even though tubular fluid and intersitium have

the same osmolarity its because water and salts are

drawn into the blood because of that balance of starling

forces where oncotic pressure here in the peritubular cap

bed was greater than hydrostatic, and that led to water

and salt reabsorption.So liquid leaving the proximal

tubule and going into the descending limb is isotonic,

even though a large proportion 60-70 percent of

everything that gets filtered got reabsorbed in the

proximal tubule, but its reabsorbed isotonically salt and

water go together. So even though the volume is much

smaller thats coming into the descending limb, its still

300mosm. As fluid goes down the descending limb, the

tonicity of the tubular fluid increases, and becomes equal

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to whatever it is in the Intersititium. The descending limb

is permeable to water, but not permeable to salt. ***

By the time that liquid reaches the loop, the bottom of

the loop, it has equilibrated with whatever the Intersitital

osm is , and so this tubular fluid as shown in this diagram

is around 1200mosm, 4 times as concenctrated as blood.

As this tubular fluid goes back up again the ascending

limb, the thin ascending is permeable to salt, so salt can

leave, but also and even more importantly the

tritransporter is located in the thick ascending limb. This

tritransporter important in establishing this osmotic

gradient within the intersitium.

Net effect is that the combined reabsorption of Na in the

thin ascending and the thick ascending leads to a fluid

that is leaving the thick ascending limb, that fluid is

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hypotonic to blood.Weve taken out a lot of salt and left

behind liquid so that now that tubular fluid is hypotonic.

This is the tubular fluid that the MD monitors , its at the

end of thick ascending limb, at the beginning of the distal

tubule. This is the fluid that the MD is monitoring.

As this fluid goes through the distal tubule, Na is

reabsorbed through the Na Cl cotransporter and very

little water can follow and so the fluid will become even

more dilute. Fig 28-4. Thats not whats shown in this

diagram, this diagram is showing what happens if there is

ADH around.

Because ADH is around there will some water

reabsorption and so this fluid becomes a little more

concentrated by the time it gets to the end of the distal

tubule and begins to go into the collecting duct. And then

as that fluid moves down the collecting duct, water and

things like urea are reabsorbed so that the fluid thats

leaving now approaches the intersitial osmolarity and you

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then make in the case of ADH being around a

concentrated low volume urine.If ADH was not around

then these segments will not be permeable to water and

so this dilute fluid coming from the distal tubule will then

just flow down through the collecting duct and leave as a

dilute high volume urine. And so adjusting the properties

of this collecting duct are important for causing you to be

able to form a concentrated urine.

Anohter way to look at what we talked about , it gives us

a more quantitative view on things. Where things happen

and where it doesnt happen.

Fig 28-7

On x axis we see diff pieces of Nephron and the urine,

from the proximal all the way to collecting duct , and

then finally ending up at the urine. X axis where we

are.

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Y axis- the osmolarity of the fluid. We have two lines.

Top mountain w/ ADH

Bottom line w/o ADH

Helping us see where ADH has an impact.

We have some numbers here. Mls that are being filtered

in one minute.

Normal GFR = 125 mls/ min. Thats where that 125

comes from , as fluid enters the proximal tubule, its

coming in at 125 mls or 125ml/min. By the time it

leaves, thers only 44 mls left.This is our 60-70 percent

that has been reabsorbed, 125ml down to 44ml.

Notice 2 things: the tonicity has not changed along that

proximal tubule so that one more time emphasizes that

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that fluid reabsorption is isotonic. Yes, we reabsorbed a

lot of liquid over 80mlsevery minute, but it was

reabsorbed isotonically. The largest amount of water and

salt reabsorption is occurring in the proximal tubule, ADH

doesnt do anything there. Whether you have ADH

around or whtehter you dont have ADH around the

largest amound of water reabsoprtion is occurring in the

proximal tubule, ADH has no effect on the proximal

tubule and so it cant make it more than 60-70 percent,

that proximal tubule is so permeable to water, so

dependent on Na reabsorption, that ADH doesnt do

anything here. So even w/ ADH around we are still

reabsorbing 60-70 percent of that fluid.

Lets follow line w/o ADH.

Now we come to the loop of henle and we see that as we

descend (dont get confused because curve isgoing up)

we are descending going down the descending limb of

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the loop of henle, water is reabsorbed along that tubule,

so water is leaving ,so therefore since salt cant follow

the osmolarity is getting higher. Thats why we went from

300 up to a little over 600 (w/o ADH). And the number at

the peak should be 25ml, so we reabsorbed some more

water along this portion of the loop of henle, along the

descending limb. Now the ascending limb is where the tri

transporter is located and so the ascending limb is

removing salt and therefore the tonicity falls, it becomes

hypotonic and in fact you can see that it becomes more

dilute than blood.Tonicity looks like it goes around

100mosm/L , to a 1/3 of what blood is. Because water

cant follow that salt the tubular volume remains the

same, still 25ml. Water went out along the descending

limb, salt went out along the ascending limb and so we

end up w/ a smaller volume, so the loop has absorbed

19ml around of water, so another 25 percent or so has

been reabsorbed in the loop of henle.

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So now this fluid continues, its dilute, continues through

distal tubule collecting duct, and if there is no ADH

around there is no opportunity for water to be

reabsorbed since the principal cells dont have aquaporin

channels in them unless there is ADH around, so that

fluid remains relatively hypotonic and maybe a little

water gets reabsorbed here in the early portion of the

distal tubule but generally we have a high voume dilute

urine in the absence of ADH.

Now lets add ADH, again ADH does nothing to the

proximal tubule so it reabsorbs its normal amount, one of

the ***ADH does it to stimulate the tritransporter, what

that does is causes the tritransporter to put more salt

into the interstitial space and increases the osmolarity of

the IS.And you can see that our max osmolarity has

gone to 1200 from where it was before (over 600), thats

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because that tritransporter amongs other things has put

in more salt, so consequently as liquid descends the thin

descending limb more water is reabsorbed, and the

tonicity approaches that in the deep medulla of the

kidney, and then along the ascending limb, we see the

tritransporter is removing that salt from the tubular fluid,

putting into the IS, and again our tonicity comes down

and is still hypotonic in the distal tubule even though

ADH is around because these portions in terms of water

permeability are unaffected or affected little by ADH

(early distal tubule, little change). So as we get to the

late distal tubule, that tubule is able to reabsorb water

and so we see the tonicity change as we go from

hypotonic to isotonic over this segment.This is affected

by ADH we got a hypotonic fluid in the distal tubule, it is

then being drawn out by the isotonic fluid in the

intersitium and we reabsorb from 25ml up to 8ml at the

end of that cortico portion of the the collecting tubule, so

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a lot of water from 25ml to 8ml , we reabsorbed in the

presence of ADH another 17ml /min in the late distal and

early collecting ductsthat are up at the cortex, So

another big piece of water reabsorption occurring there

when ADH is around.

Now this small volume of tubular fluid that is isotonicis

moving through the portion of the collecting duct that

goes through the medulla , through the deeper portions

of the kidney where the intersititial fluid is now

hypertonic, and so in the presence of ADH those principal

cells in the medullary collecting duct are permeable to

water, so water leaves, and we get even more

concentrated urine (high osmolarity) that is of even a

smaller volume (.2ml).

So now weve reabsorbed all but .2ml of that fluid that

was left, so the final urine volume will be small and the

tonicity will be high.

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In the presence or absence of ADH, lot of water

reabsorbe in the proximal tubule.

In the presence of ADH, we get enhanced water

reabsorption along the descending limb of the loop of

henle, we get enhanced water reabsorption in the late

distal and the cortico collectin duct, and we get enhanced

water reabsorption in the medullary collecting duct.

So proximal tubule reabsorbs the largest amount ,

followed by the descending limb of the loop of henle,

then the late distal cortico collecting duct, and finally the

medullary collecting duct tops things off.

Proximal tubule bigger than any other areas for

reabsorption of water.

Fig 38-17

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Understand why numbers change.

Several things happen simulatenously, well discuss one

at a time.

We got some things that influence and help us make this

osmotic gradient. Our goal is to explain how we have this

gradient in osmolarity starting close to isotonic near the

top portion of the medullary collecting duct or loop of

henle, and how it gets more concentrated in the

intersititum at the tip.

One, is the structure , these are things that are important

for generating this osmotic gradient.

1. Structure, you have to have a loop, lf you dont have a

loop you cant make this happen.

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Length loop and length of loop. The longer the loop, the

bigger the gradient you can make. Desert rats that get all

water from nuts, have very long loops of henle.

Body cannot adjust length. We have a fixed loop length

but length is imp.

2. Flowfluid is always moving through the tubular fluid,

through the loop of henle, so that constant flow of fluid is

important in helping to establish the gradient. And you

know from autoregulation that the kidney tries to keep

GFR fairly constant, so that fluid movement through the

tubules is relatively constant so that enables then the

loop of henle to have just a constant flow of fluid so the

flow is imp.

3. Permeability properties-so the descending limbs of the

loop of henle, have a different water and salt

permeability than the ascending limb, descending

permeable to water, not to salt. Ascending permeable

to salt, not to water. That diff in perm prop imp.

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4. Tritransporter responsible for the initital event, the

primary action that then enables all other things to occur

subsequently.

Structure fixed

Perm fairly fixed

Flow isnt

Tritransporter- well talk about how it works.

Loop A

Here we have the thin descending limb and the thick

ascending limb, and we have in middle and all over the

medullary instersitium.

We start out with tubular fluid coming from the proximal

tubule filling the loop of henle, and that fluid is isotonic.

300 everywhere. And 300 in the MI.Initial position.

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The tritransporter located on the asencding thick limb,

pumps salt out of the tubular fluid and puts it into the

intersititium. That tritransporter pumps until there is a

difference in conc. of 200mosm.It is able to establish

that difference, if the intersititum becomes bigger than

that 200 diff, that means some salt will go back in other

direction and the tritransporter will try to kick it out ,

were in a steady state btwn what can come back and

what it can pump against, but it can establish a diff of

200mosm.

If we just start w/ first line , we see that this 300 btwn

the tubular fluid in the ascending limb and the I. So the

tritransporter can make this becomes 200 different so we

get that here (1stline B). But as soon as this osm begins

to go up, then water will leave the fluid in the thin

descending which will dilute this a little bit which will

mean the tritransporter will pump out some more salt,

which will mean some water will leave from the

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descending limb , and finally we reach a condition where

were in some kind of steady state w/ a 200mosm diff

across the ascending limb and equality across the

descending limb.And since we have 300 all through

here, we will have the same situation once weve reached

a steady state. Important thing was we had this

tritransporter that could establish that gradient, water

couldnt follow, so the permeability propoerties of the

ascending limb help that to establish that osmotic

gradient and then the water perm of the descending

enable the descending tubular fluid to equilibrate w/ I

fluid. We still havent made a gradient.

So nothing stays the same , changes, so tubular fluid

comes in from proximal tubule, Now we have fluid

entering and so we have little boxes coming in at 300

displacing the boxes that were at 400. That moves the

stuff around and pushes these guys up at the other side,

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and so the tritransporters says I dont have a 200

gradient, its only 100 , so it pumps and estabilishes a

200mosm diff btwn 2 sides, and now the fluid in the

descending limb leaves to try to make equilibration and

we start seeing 500 in the bottom and 350 top. So a little

bit of introduction of fluid displaced relationships btwn IF

and tritransporter responsible for establishing this

gradient, so flow is imp because it looks like bringing in

new fluid thats isotonic upsets the balance which makes

us pump some more it has displaced fluid that was a little

hypertonic into an area where its even more hypertonic

and this and the tritransporter keeps that gradient going.

So now we have a new steady state, I is 350 at the top ,

500 near the tip , we see the descending limb is

hypertonic ascending limb is hypotonic as it goes towards

the top ,and this fluid is hypotonic and will be going on to

the distal tubule. So one more time, we get some more

isotonic fluid from the proximal tubule, it equilibrates

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with the IF, water leaves diluting IF, we no longer have a

200 mosm gradient across the wall of the thick ascending

so the tritransporter kicks in , establishes this gradient,

fluid in the descending limb equilibrates and it looks as

though were making an even bigger gradient now were

at 325, 600 at the tip (Diag F). We introduce a little more

fluid, pushes everyone around and as last chart implies

we can then generate situation where we can get a nice

steep gradient through the action of fluid flowing through

the loop, the different permeability properties btwn the

des and as limb as well as action of tritransporter to be

able to establish and maintain a concentration gradient

across the walls of the thick ascending limb, so thats

how the Intersitial gradient is established through these

things. Now the purpose then of the loop of henle is to

make that gradient, the liquid thats leaving is hypotonic

all the time, so the loop of henle isnt concentrating the

urine , its in fact diluting the urine , and that salt that has

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left that fluid is being put in the I space, and the next

step willl be the use of that fluid, or osmotic gradient to

reabsorb water and thats where the collecting duct

comes in. So collecting duct passing through the same

area where its 312 at top and 700 at bottom. So here is

our dilute fluid going down the collecting duct, so the

collecting duct is passing through this medullary area

where there is this high osmotic intersitium, and if there

is ADH around water can leave and therefore lead to a

small volume concentrated urine. So the collecting duct

within the medulla makes use of the osmotic gradient

that the loop of henle generated.So again the structures,

the relationship btwn the loop, the intersititum, and these

medullary collecting ducts is important, so the loop

makes the gradient , the collecting duct uses the gradient

in the presence of ADH.

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Understand Process. What things are impo to make

gradient, which structure makes gradient, how this

gradient used by other struct.

Multiplication because it got bigger

Countercurrent flow going in two diff directions

Countercurrent multiplication is what happens w/ the

loop of henle and the intersitium, countercurrent

exchange is what happens in the vasa recta.

So back in this diagram we had loop and collecting duct,

we also have vasa recta, other capillary bed that supplies

nutrients and removes waste and salts and water from

this meudllary area.

Diag 38-18

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We see that intersitium is here around 1200 at the tip

and is some 300 in the cortex.

We need to supply those epithelial cells of the loop of

henle and of the collecting duct w/ nutrients and we

need to take away their waste, we have blood that we

know is isotonic 300mosm, so how can we bring this

liquid blood into the area around the loop of henle (tip)

and collecting duct, have a capillary bed where things

freely exchange back and forth and not wash away that

salt.

So if we had a BV coming in straight in here at 300 and

there was exchange w/ this hypertonic fluid, the

bloodleaving will be 1200mosm, and the capillaries will

provide nutrients but the poor ascending limb worked so

hard to establish this osmotic gradient, and now were

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bringing blood in thats going to wash away that gradient

and take it back to the body , we need a process that

prevents that or minimizes it.

So again we use a loop, countercurrent relationship here.

So blood is coming in into vasa recta at 300, this is now a

capillary bed so its freely permeable to salt and water

and so as the blood passes down the descending portion

of the vasa recta moving into the tip of the loop of henle,

it equilibrates , salt and water move appropriately, it

equilibrates w/ the intersitium. And so as this diag

implies, it reaches the same tonicity as the intersitium, if

this blood were now to leave from the medulla of the

kidney it will carry blood away at 1200 mosm but instead

it goes back up the ascending side of the vasa recta and

the opposite happens salt and water requilibrate and the

blood now leaving and going into a vein is now slightly

hypertonic (325) but certainly not as hypertonic as it had

been down at the tip, so this countercurrent exchange

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because all were doing is exchanging salt and water,

enables us to perfuse deep within the medulla, perfuse

w/ blood structures deep within the medulla, w/o

removing very much salt. Yes, a little bit of salt left, so

its a little hypertonic, but not as bad as it could have

been.

So thats countercurrent exchange which is the process

used by the vasculature to provide perfusion w/o washing

the salt away. Same structure in skin. Not unique to

kidney, but imp because it enables perfusion of

structures w/o loss of salt.

If we were to increase blood flow, then this exchange will

not be as complete because all of the movements require

time. So more salt will be lost. Increase blood flow =

causes increased salt lost from the medullary I.

Increased blood flow would be detrimental to producing a

low volume urine because w/ increased blood flow more

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salt will be washed away , the I will not be at 1200, will

be less, and so body couldnt reabsorb as much water.

The times that we have increased blood flow, such as

increased MAP, is just the right time we want to make

more urine. If we have an increase in MAP, one way to

lower and bring MAP back to normal is to make more

urine. Increasing vasa recta bloodflow will wash away

some of those salts, reduce the osmotic gradient from

the cortex to the medulla within the I, and therefore

reduce how much water gets reabsorbed so that will go

into urine and be lost from the body , and help bring bp

down. When we have a fall in MAP, we reduce vasa recta

bloodflow, that enables less salt to be removed, therefore

helps to concentrate urine better.

So loop of henle responsible for the gradient, collecting

duct makes use of that gradient, the process within the

loop of henle that generates that gradient is

countercurrent multiplication, requires different

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permeability properties btwn asc and desc limbs to salt

and water, requires the loop config, requires flow, and

requires the tritransporter.

The vasa recta also organized in loop config in order to

perfuse but not wash out too much salt. So we have

countercurrent exchange rather than countercurrent

multiplication.

Tritransporter always working so always on osmotic

gradient in MI, ADH just makes it go faster, always

pumping along.

One more thing,

Urea is the way body gets rid of N, not a toxic subs, just

a way the body combines a couple of Ns and excretes it.

Urea has interesting properties, but it also plays imp role

in helping to increase the osm here in the I. Other thing,

its movement across cell membranes is sensitive to ADH,

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so its also regulated by ADH.So this little diagram vasa

recta coming in, loop of henle, collecting duct, close

together.

Numbers in tubule represent the percent of urea that is

starting, we start w/ 100 percent of urea. We filter urea,

urea is freely permeable through cell membranes,unless

theyre not. 300mosm solution of urea is isoosmotic but

not isotonic, because for most cells urea is clearly

permeable.So we filter Urea so 100 percent or the same

conc of urea thats in the blood enters the proximal

tubule , and as that fluid passes through the proximal

tubule, half of the urea is reabsorbed , just through

channels, passively. That fluid then stays 50 percent, so

not much urea leaves during the descending limb and in

fact, urea is actually added back to the tubular fluid on

the ascending limb, such that the fluid leaving the

ascending limb actually has more urea in it than the fluid

that entered the proximal tubule , so if you add those

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numbers 60 (from collecting duct) +50 =110, this diag

showing us that 60 percent more urea is added by

secretion in the asc limb of LH, which then makes the

urea conc greater in the tubular fluid than it was in the

proximal tubule. From here on, through the distal tubule

and the cortico collecting ducts these cells are

impermeable to urea. So urea cant leave, and you know

water and stuff move back and forth. So fluid coming into

the medullary collecting duct has a high urea

concentration.In the cortico collecting duct and late

distal, water could be reabsorbed so that would help to

further concentrate the urea. So the urea conc entering

the medullary collecting duct is high. What happens as it

passes down the collecting duct, is this portion of the

collecting duct is now permeable to urea and is even

more permeable if ADH is around. So because the urea

conc in this tubular fluid is high relative to the I, urea

leaves and that high urea conc. in the I is what is

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enabling the secretion of urea into this ascending limbso

we generate a gradient for urea to go from the medullary

collecting duct fluid into the I , from the I into the

ascending limb and so some of the urea essentially just

cycles it reeneters the tubular fluid in the ascending limb,

gets concentrated as it passes along the distal and

cortico collecting duct and then is reabsorbed in the

medullary collecting to be re secreted into the thin

ascending limb.Some of it a little bit also gets taken up

by the vasa recta and returned to the body. So theres a

urea cycle here that enables secretion , reabsorption to

occur through this medullary area of the kidney.When

urea leaves water follows. ( HELPS US CONCENTRATE

URINE) The two of them go together, what happens then

is the osmolarity here is diluted a little by that water that

has left the collecting duct w/ urea which enables more

Na Cl , its diluting the osmolarity , which enables Na CL

to be added from the thin ascending through a passive

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process and helps to add osmotic particles to this MI

fluid.So the presence or the movement of urea and

water out of the collecting duct dilutes some of this

osmolarity enhancing Na CL reabsorption from the thin

asending that helps to put more salt there to further

enhance water reabsorption and this is enhanced further

by ADH, so ADH increases water permeability and

increases movement of Urea into that space. Which is

then able to draw Na and Cl from the thin asc limb and

keep the osmolarity high and further enable water

reabsorption, if that didnt occur we wouldnt get this

additional Salt being added and the concentrating ability

will be impaired.

So this an example of a molecule that is moving back and

forth both reab, secretion, just through passive

properties.But urea there plays an important role in

helping us form a conc. urine.

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Factors

Things that willlimit your ability to form a concentrated

urine or to make a small volume urine.

1. Obviously the presence of absence of ADH.

In the absence of ADH, the tritransporter doesnt work as

hard, the late distal and collecting ducts are not

permeable to water, and so the fluid that is leaving the

distal tubule is hypotonic and it stays that way as it goes

down thorough the late distal and into the collecting

ducts.In the absence of ADH, there is little water

reabsorption large volume urine. This could be because

ADH isnt released from hypothalamus or it could be

because ADH doesnt work properly on receptors. No

release, or it cant work effectively.

2. Another thing that will affect ability to form a

concentrated urine is the activity of the tritransporter.A

lot of diuretics act here, the most potent ones are loop

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diuretics, and they inhibit the tritransporter which means

that this osmotic graient cannot be established LH cannot

do whats its supposed to do, and so you lose salt and

water because of that.

3. Vasa recta blood flow. We talked about vasa blood flow

and how that blood leaving that vasa recta is slightly

hypertonic and so if that bloodflow goes higher then

more salt will be lost, generally the vasa recta bloodflow

is relatively small, but it can be regulated under

conditions where we want to conserve water, or where

we want to remove water.

4. Increased tubular flow. The faster the fluid flows

through those tubules , from descending through

ascending the less were able to form a concentrated

urine.Time is important, the tritransporter has to move

those molecules , the fluid in the descending limb has to

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equilibrate w/ whatever the osm is in the MI, so if the

fluid is moving through those tubules too rapidly , those

gradients cant get established , therefore osmotic

gradient in the I is reduced, and thats one of the things

that a diuretic does, it causes more tubular flow,so if we

had a diuretic that acted in the loop then that would

increase loop flow, if we had a diuretic that worked even

further proximal, in the proximal tubule by increasing the

tubular flow will reduce the osmotic gradient and that will

affect the ability to form a concentrated urine.

5. Increased in GFR will push more fluid through there at

a faster rate, so increases in MAP will increasse GFR

because of an increase in glomerula capillary pressure so

more fluid will filter through, high tubular flow ratewill

mean less time to form that gradient and will make a

dilute urine.

6. If we have any molecules that act as osmotic agents ,

glucose generally gets reabsorbed completely in the

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proximal tubule by that transport process, Na Glucose

cotransporter,which has Tm , transporter maximum, but

if that transport max is exceeded, then glucose is left in

the tubular fluid, it doesnt get reabsorbed in later

portions such as in collecting duct or late distal, so its

holding water, that water only trying to equilbrate w/ I.

If the tubular already hypertonic because lot of glucose

there, then that equilibration wont be as thorough and so

any osmotic particles will be to increase urine formation

which is called osmotic diuresis.

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